The ability of macrophages to release hydrogen peroxide is probably the first correlate of macrophage activation which has been shown to be both: (a) increased in macrophages with enhanced antitumor and antimicrobial activity; (b) low in macrophages with low levels of antitumor and antimicrobial activity; (c) in itself capable of antitumor and antimicrobial activity, which in some cases is sufficient to account for the activity of the macrophages; and (d) defined and quantifiable at a biochemical level. The objective of the work proposed here is to extend these findings. Such studies will seek to learn whether antibody-dependent cell-mediated cytoxicity by macrophages, and T cell-mediated cytotoxicity have an oxidative basis; how tumor cells resist different oxidative species; whether peroxide-resistant variants can be selected; whether tumors suppress macrophage oxidative responses; whether H2O2 can kill tumor cells in vivo; whether certain new agents trigger H2O2 release from activated macrophages; and whether the oxidative response of leukocytes may activate certain cancer chemotherapeutic drugs. Human studies will focus on improved methodology for collection of blood monocytes and emigrated mononuclear phagocytes from skin windows, comparing their oxidative and antitumor responses before and after activation by lymphocyte mediators. Biochemical studies will attempt to localize and partially characterize the oxidase, and explore the prolonged kinetics of the oxidative response, in macrophages.